Might adrenergic alpha2C-agonists/alpha2A-antagonists become novel therapeutic tools for pain treatment with morphine?

J Med Chem. 2009 Nov 26;52(22):7319-22. doi: 10.1021/jm901262f.

Abstract

The imidazoline nucleus linked in position 2 via an oxyethylene bridge to a phenyl ring carrying an ortho substituent of moderate steric bulk provided alpha(2)-adrenergic (AR) ligands endowed with significant alpha(2C)-agonism/alpha(2A)-antagonism. Similar behavior was displayed by cirazoline (12). For their positive morphine analgesia modulation (due to alpha(2C)-AR stimulation) and sedation overcoming (due to alpha(2A)-AR antagonism), 8 and 11 might be useful as adjuvant agents in the management of pain with morphine.

MeSH terms

  • Adjuvants, Pharmaceutic / pharmacology
  • Adrenergic alpha-2 Receptor Agonists*
  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic alpha-Agonists / pharmacology*
  • Adrenergic alpha-Antagonists / pharmacology*
  • Analgesics / therapeutic use*
  • Animals
  • CHO Cells
  • Clonidine / pharmacology
  • Cricetinae
  • Cricetulus
  • Drug Discovery
  • Humans
  • Imidazoles / pharmacology
  • Morphine / therapeutic use*
  • Pain / drug therapy*
  • Pain / metabolism
  • Receptors, Adrenergic, alpha-2

Substances

  • ADRA2A protein, human
  • Adjuvants, Pharmaceutic
  • Adrenergic alpha-2 Receptor Agonists
  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Analgesics
  • Imidazoles
  • Receptors, Adrenergic, alpha-2
  • Morphine
  • Clonidine
  • cirazoline